For natural selection, there must be mechanisms that create phenotypic diversity, presumably from relatively simple molecular changes in an organism. Peisajovich et al. tested the extent to which changes in phenotype can occur by systematic swapping of protein domains in the components of the biochemical signaling pathway that controls mating in yeast. Such changes decreased or increased responsiveness to yeast mating pheromone, and some translated into changes in mating efficiency. The authors propose that shuffling of modular protein domains may be an important source of phenotypic diversity in evolution and may also be a useful strategy for the engineering of biological systems.